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Interactions of the ectodomain of HFE with the transferrin receptor are critical for iron homeostasis in cells
Author(s) -
Roy Cindy N.,
Carlson Eric J.,
Anderson Emily L.,
Basava Alivelu,
Starnes Steven M.,
Feder John N.,
Enns Caroline A.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02173-6
Subject(s) - ectodomain , ferritin , transferrin receptor , hereditary hemochromatosis , transferrin , hemochromatosis , mutation , chemistry , signal transduction , microbiology and biotechnology , wild type , receptor , hepcidin , biology , biochemistry , genetics , immunology , mutant , gene , inflammation
Expression of wild type HFE reduces the ferritin levels of cells in culture. In this report we demonstrate that the predominant hereditary hemochromatosis mutation, C282Y 2 HFE, does not reduce ferritin expression. However, the second mutation, H63D HFE, reduces ferritin expression to a level indistinguishable from cells expressing wild type HFE. Further, two HFE cytoplasmic domain mutations engineered to disrupt potential signal transduction, S335M and Y342C, were functionally indistinguishable from wild type HFE in this assay, as was soluble HFE. These results implicate a role for the interaction of HFE with the transferrin receptor in lowering cellular ferritin levels.